Bioreducible Polymeric Carriers for Controlled Peptide Release
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Solution Overview
Problem
Existing delivery systems face challenges in effectively, safely, and controllably releasing sensitive biomolecules such as peptides and siRNA, lacking advancements similar to those seen for small molecule drugs.
Innovation Solution
Development of bioreducible, hydrolytically degradable polymers and nanoparticles, microparticles, and gels for controlled release of therapeutic agents like peptides and siRNA, utilizing mechanisms like hydrolytic and enzymatic degradation, and disulfide reduction, with tunable release profiles and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional delivery systems are used for peptides and siRNA, then the systems lack controlled release capability, but developing new bioreducible polymer systems increases device complexity
Solution Approach 1:
The patent employs parameter changes by modifying polymer composition (incorporating disulfide bonds, ester linkages, and PEG chains) and molecular weight (5-100 kDa range) to achieve controlled release kinetics. The bioreducible polymer system uses可调 parameters like disulfide bond density and hydrophobic/hydrophilic balance to control degradation rate and drug release profile, resolving the contradiction between reliability and complexity.
Solution Approach 2:
The invention uses composite materials by combining multiple polymer components (bioreducible segments with disulfide bonds, hydrolytically degradable ester linkages, and PEG chains) into a single delivery system. This composite approach enables simultaneous controlled release through multiple degradation mechanisms while maintaining system manageability through standardized nanoparticle formulation.
2Speed
If rapid release of therapeutic agents is achieved, then treatment speed improves, but stability and controlled release are compromised
Solution Approach 1:
The patent applies dynamics by creating a time-dependent release system where the polymer maintains stability initially through stable disulfide bonds and ester linkages, then dynamically transitions to rapid release as these bonds degrade biologically. The system adapts its release rate over time, starting slow for stability and accelerating as degradation occurs, resolving the contradiction between speed and stability.
Solution Approach 2:
The invention converts the potentially harmful rapid degradation of polymers into a beneficial controlled release mechanism. By incorporating bioreducible disulfide bonds that degrade in response to intracellular glutathione, the system transforms what would be unstable rapid breakdown into a controlled, triggered release event that benefits therapeutic efficacy while maintaining pre-delivery stability.
3Stability of the object's composition
If polymeric delivery systems are used to protect biomolecules, then stability improves, but cytotoxicity may increase
Solution Approach 1:
The patent uses parameter changes to reduce cytotoxicity while maintaining stability by adjusting polymer molecular weight (5-100 kDa), PEG chain length, and hydrophobic/hydrophilic balance. These parameter optimizations ensure the polymer protects biomolecules sufficiently during delivery but degrades into non-toxic components (amino acids, PEG fragments) at the target site, resolving the contradiction between stability and cytotoxicity.
Solution Approach 2:
The invention applies discarding and recovering by designing the polymer to discard its protective function after delivery through biological degradation. The bioreducible disulfide bonds and hydrolytically labile ester linkages cause the polymer to break down into harmless fragments that are eliminated by cellular metabolism, allowing the system to provide stability during transport then safely discard itself at the destination, resolving the stability-cytotoxicity contradiction.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
Facilitates targeted and controlled delivery of therapeutic agents, enhancing efficacy for conditions like cancer and age-related macular degeneration, with improved stability and reduced cytotoxicity.
Implementation Method 1
utilizing mechanisms like hydrolytic and enzymatic degradation, and disulfide reduction
Implementation Method 2
utilizing mechanisms like hydrolytic and enzymatic degradation
Implementation Method 3
utilizing mechanisms like hydrolytic and enzymatic degradation
Data Source
AI summary
Polymeric nanoparticles, microparticles, and gels for delivering cargo, e.g., a therapeutic agent, such as a peptide, to a target, e.g., a cell, and their use for treating diseases, including angiogenesis-dependent diseases, such as age-related macular degeneration and cancer, are disclosed. Methods for formulating, stabilizing, and administering single peptides or combinations of peptides via polymeric particle and gel delivery systems also are disclosed.